Biology subjects

Gretton, D.

Publications and source records attributed to Gretton, D..

3 recordsLinked to original sources

bioRxiv2026

Complementing Biosafety Levels With Societal Safety Levels

Biosafety level (BSL) classifications of biological agents have succeeded at minimizing occupational risk inside laboratories, but largely neglect the potential for onward transmission. As a result, many non-transmissible pathogens that could kill at most one individual per person exposed require greater containment than 1918 influenza, a virus that killed 50-100 million and might cause a new pandemic today. Laboratory workers are consenting professionals; the public is not. We recommend complementing BSLs with explicit thresholds for expected societal harm. Here we formalize Societal Safety Levels (SSLs) based on expected public fatalities per year, which we quantify from (i) estimated probability of laboratory release, (ii) likelihood of societal transmission, and (iii) consequence. SSLs would apply specifically to laboratory research with replication-competent potential pandemic pathogens, and would not restrict field surveillance, sequencing, or countermeasure development using non-replicating systems or pandemic-incapable agents. We find that applying the 0.1 expected deaths per facility-year standard common across multiple major-hazard industries to potential pandemic pathogen research would require marked safety improvements. Complementing BSLs with SSLs would establish enforceable accident-safety thresholds for pandemic-capable pathogens, bringing high-risk biological research into alignment with the quantitative safety standards that help other hazardous industries operate with public acceptance.

microbiology↗

bioRxiv2024

Random adversarial threshold search enables automated DNA screening

Custom DNA synthesis underpins modern biology, but controlled genes in the wrong hands could threaten many lives and public trust in science. In .1992, a virology-trained mass murderer tried and failed to obtain physical samples of Ebola; today, viruses can be assembled from synthetic DNA fragments. Screening orders for controlled sequences is unreliable and expensive because current similarity search algorithms yield false alarms requiring expert human review. Exact-match search can achieve perfect specificity among short known sequences by detecting subsequences unique to controlled genes, but can be trivially evaded by incorporating mutations. Here we rescue exact-match search by additionally screening for predicted functional variants of pseudo-randomly chosen subsequences that arent found in known unregulated genes. To experimentally assess robustness, we protected nine windows from the M13 bacteriophage virus, then invited a "red team" to launch up to 21,000 attacks at each window and measure the fitness of their designed mutants. We identified defensible windows from regulated pathogens, built a test database that our experiments indicate will block 99.999% of functional attacks, and verified its sensitivity against redesigned enzymes. Exact-match search with functional variant prediction offers a promising way to safeguard biotechnology by automating DNA synthesis screening. SummarySearching for exact matches to pre-computed functional variants unique to controlled genes enables sensitive, secure, and automated DNA synthesis screening.

synthetic biology↗

bioRxiv2020

A high-throughput platform for feedback-controlled directed evolution.

Continuous directed evolution rapidly implements cycles of mutagenesis, selection, and replication to accelerate protein engineering. However, individual experiments are typically cumbersome, reagent-intensive, and require manual readjustment, limiting the number of evolutionary trajectories that can be explored. We report the design and validation of Phage-and-Robotics-Assisted Near-Continuous Evolution (PRANCE), an automation platform for the continuous directed evolution of biomolecules that enables real-time activitydependent reporter and absorbance monitoring of up to 96 parallel evolution experiments. We use this platform to characterize the evolutionary stochasticity of T7 RNA polymerase evolution, conserve precious reagents with miniaturized evolution volumes during evolution of aminoacyl-tRNA synthetases, and perform a massively parallel evolution of diverse candidate quadruplet tRNAs. Finally, we implement a feedback control system that autonomously modifies the selection strength in response to real-time fitness measurements. By addressing many of the limitations of previous methods within a single platform, PRANCE simultaneously enables multiplexed, miniaturized, and feedback-controlled continuous directed evolution.

bioengineering↗